AB0175 EVALUATION OF THE STATE OF ACTIVATION OF PERIPHERAL BLOOD MONONUCLEAR CELLS IN PATIENTS WITH POLYMYALGIA RHEUMATICA
Authors: C. Castellani, S. Colafrancesco, C. Barbati, S. Truglia, G. Buoncuore, R. Priori, A. Sili Scavalli, E. Molteni, G. Sciarra, L. Di Sanzo, G. Bevignani, F. Conti, R. Scrivo
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Polymyalgia rheumatica (PMR) is a chronic inflammatory disease that affects individuals of 50 or more years of age. It is characterised by shoulder and pelvic girdle pain, morning stiffness, functional limitation, and an increase in inflammatory indexes. Glucocorticoids (GC) represent the cornerstone of treatment. The pathogenesis is still not completely understood, although many shreds of evidence show the role of innate immunity. <h3>Objectives</h3> To evaluate whether peripheral blood mononuclear cells (PBMCs) of patients with newly diagnosed PMR and not yet treated with GC show a baseline activation that is affected by treatment with GC. <h3>Methods</h3> We carried out an observational study, enrolling patients with PMR (2012 EULAR/ACR criteria) not yet treated with GC and controls. Blood samples were obtained from patients at baseline (T0) and after 4 months since the beginning of GC (T4), and from controls. An ultrasound (US) of shoulder and pelvic girdles was performed in PMR patients at T0 and T4. Demographic, clinical and US results were recorded in an electronic database. Patients with a personal history of rheumatic, inflammatory or oncologic diseases or subjects that received such a diagnosis during the study were excluded. PBMCs were isolated by density gradient centrifugation and analyzed in triplicates, among which one was stimulated with lipopolysaccharide (LPS). Then, the supernatant was collected and ELISA was performed for the determination of IL-1β, TNF, and IL-6 levels. The same cytokines were searched in the sera of PMR patients at T0 and at T4 and in the controls. <h3>Results</h3> We consecutively enrolled 8 patients with a new diagnosis of PMR (F/M 6/2; median age/IQR 73/9.75 years; median disease duration 2/2.75 months) and 8 individuals without PMR matched for gender, age, and comorbidities with PMR patients (F/M 6/2; median age/IQR 69/10.5 years). We found higher concentrations of IL-1β and IL-6 in the unstimulated supernatant of PMR patients at T0 compared to T4 (p=0.0313 for both) (Figure 1A-B). Higher TNF levels were found in the unstimulated supernatant of PMR patients at baseline compared to controls (p=0.0127). Surprisingly, IL-6 levels in the stimulated supernatant of PMR patients at T0 were lower than those of controls (p=0.0426). No significant differences were found in the serum levels of IL-1β and TNF, while IL-6 levels in the sera of PMR patients at baseline were higher compared to those of the control group (p=0.0123). <h3>Conclusion</h3> PBMCs of PMR patients seem to be activated at baseline compared to controls. Our data indicate a possible role of immunosenescence or an "exhaustion" of PMBCs, that could be constitutively activated and not prone to responding to further stimuli, such as LPS. Moreover, we observed higher serum levels of IL-6 in PMR patients. More studies are needed to confirm the role of PBMCs and inflammatory cytokines in the pathogenesis of PMR. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.